The establishment and maintenance of pregnancy requires the coordinated activity of a highly specialized maternal tissue: the decidua. Extensive investigation from our laboratory has revealed that one important function of rat decidual cells is their hormone-producing capabilities. We have shown that a defined decidual cell population in the decidua acts as an endocrine gland and secretes hormone related to pituitary and ovarian hormones; decidual PRL-related protein, activin and follistatin. Another defined cell population expresses in abundance alpha2 macroglobulin, a known activin-binding protein and a potent protease inhibitor. The overall objective of our research is to understand the involvement of the decidual cell signaling system in the establishment and maintenance of pregnancy. The focus of this grant is to define the regulation and interactions of these decidua-derived proteins and their role in the maintenance of the right milieu for fetal development. The first specific aim centers on the expression of decidual PRL-related protein and its role both in the decidua and in the corpus luteum. We will express dPRP in insect and bacterial cells and examine the role of this hormone on the production and action of key proteins involved in progesterone metabolism and protein synthesis. The second aim will focus on the regulation and function of the decidual alpha2 MG gene expression and determine whether alpha2 MG binds to and protects the decidual PRL-related protein from degradation. We will also investigate whether a key role of alpha2 MG is to bind to activin and prevent activin A induced apoptosis. Finally, in the third aim we will test the hypothesis that the decidual cells have an intrinsic ability to secrete activin A and that activin A stimulates the expression of its own gene and induces apoptosis, leading to the regression and reorganization of the decidua which is essential for normal fetal development. We will also test the possibility that during development alpha2 MG and FST, two decidua-derived activin A binding proteins, prevent activin action and direct when and in which cell activin is to be expressed.